Alana Cutland

Mr Tom Osborne 
Senior Coroner  
HM Coroner’s Office 
Civic Offices 
1 Saxon Gate East 
Central Milton Keynes 
MK9 3EJ 
By Email: Coroners.office@milton-keynes.gov.uk 

MHRA 
10 South Colonnade 
Canary Wharf 
London 
E14 4PU 

www.gov.uk/mhra 

27/10/2020 

  Dear Mr Osborne 

RE: Regulation 28 Report concerning Alana Molly Cutland (doxycycline) 

Thank you for your letter dated 5 August 2020, in which you asked the MHRA to provide a response 
to the Regulation 28 Report to Prevent Future Deaths following the inquest into the tragic death of 
Miss Alana Cutland.  

Your report identified the following matters of concern which fall within the remit of the MHRA. 

1. The patient experienced a psychotic reaction as a result of taking doxycycline and there was 
no mention of the possibility of this in the patient leaflet. If the patient or her parents had been 
aware of this possible side effect, they might have been able to intervene earlier to avoid her 
death. 

2. The information sent out with doxycycline should be reviewed. 

The MHRA as a regulatory agency has a responsibility to ensure that medicines are efficacious and 
acceptably safe, and that any possible side effects which have been recognised to occur with use of 
a medicine are appropriately described in the authorised product information (Summary of Product 
Characteristics, labelling and Patient Information Leaflet, PIL). 

As you have noted, the product information for doxycycline does not mention psychotic reactions as 
a possible side effect. We have conducted a review of the available evidence concerning doxycycline 
and  psychotic  reactions  and  sought  expert  advice  from  the  Commission  on  Human  Medicine’s 
Pharmacovigilance  Expert  Advisory  Group  on  the  strength  of  the  evidence  and  whether  the 
doxycycline product information should reflect these events. 

As you will be aware, doxycycline has been widely used in the UK since the 1960s for the treatment 
of various bacterial infections, skin conditions such as acne and as an antimalarial drug. Aside from 
Miss  Cutland’s  case,  as  of  2nd  September  2020,  the  MHRA  have  received  five  other  reports  of 
doxycycline and psychotic disorder, all concerning doxycycline use for bacterial infections. Three of 
the  cases  offer  possible  alternative  explanations  for  the  events,  either  due  to  previous  psychiatric 
history  or  concomitant  medications  that  are  themselves  associated  with  psychotic  reactions.    It  is 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 acknowledged that Miss Cutland did not appear to have any history of psychiatric illness, and no other 
medication was reported. However, her case contains limited details on which to base an assessment 
of causality with doxycycline.  

Overall,  these  spontaneous  ADR  reports  provide  limited  evidence  on  which  to  base  a  thorough 
assessment  of  causality  between  doxycycline  and  psychotic  reactions.  While  under-reporting  is  a 
common problem with spontaneous ADR reporting, given that in the context of malaria prophylaxis, 
doxycycline is often given to healthy people, it may be that we would expect to see more cases of a 
serious  reaction  like  psychosis  if  it  were  a  true  ADR  for  doxycycline.    In  addition,  there  is  no 
established  biological  mechanism  to  explain  an  association  between  doxycycline  and  psychotic 
reactions and there is little in the way of published literature suggesting a causal link, including a lack 
of any well-controlled studies.  

The CHM Pharmacovigilance Expert Advisory Group advised that overall, the evidence to support a 
causal  association  between  doxycycline  and  psychotic  disorder  was  limited  considering  the 
cumulative  exposure  to  this  drug  in  the  UK  which  is  likely  to  be  in  the  order  of  tens  of  millions  of 
people.  The  PEAG  advised  that  prior  to  the  possible  addition  of  psychotic  type  reactions  in  the 
doxycycline product information, which may cause patient alarm, further data is needed to enable a 
more robust assessment. The EAG recommended that the marketing authorisation holder (MAH) for 
the brand-leader doxycycline product should be requested to propose how this additional data may 
be  collected,  for  example  by  investigating  the  feasibility  of  conducting  a  study  using  electronic 
healthcare records which compares rates of psychotic reactions following doxycycline, with another 
antibiotic. 

Action being taken by the MHRA 

In  summary,  we  have  considered  the  limited  available  evidence  on  doxycycline  and  psychotic 
reactions  and,  based  on  expert  advice 
the  Commission  on  Human  Medicine’s 
from 
Pharmacovigilance Expert Advisory Group, will request that the lead MAH submits a proposal by 30 
November 2020 to gather further data on the risk of psychotic reactions following doxycycline. 

For your information, Miss Cutland’s case has been recorded on our adverse drug reaction database 
with the Yellow Card reference number ADR 24432232. 

I will update you once we have evaluated the response of the lead MAH. 

In the  meantime,  we  will  continue to keep  the  issue  of  doxycycline  and  psychotic  reactions  under 
close review.  

Yours sincerely 

Dr 
Chief Executive, MHRA